The natural biology of the complex group of murine C-type RNA viruses is being studied using virological, genetic, and biochemical approaches. Continuing studies of the genetic transmission of both ecotropic and xenotropic virus classes have led to the chromosomal mapping of additional virus-inducing loci. Studies of the recombinant MCF viruses in relation to murine leukemogenesis have delineated certain biological and biochemical correlates of the ability of a given MCF isolate to induce or accelerate leukemia, leading to the recognition of target tissue host range as the major determinant of leukemogenicity. Sensitivity to MCF virus infection has been shown to be under genetic control and the relationship to lymphoid erythroid neoplasia of MCF virus infection, spread and/or generation is under study. Endogenous virus genomes in various inbred and wild mice are being analyzed using defined biochemical probes derived from molecular cloning of ectropic, xenotropic and MCF viruses; these include cross-reactive and ectropic and xenotropic specific viral genome fragments.